Site-oriented conjugation of poly(2-methacryloyloxyethyl phosphorylcholine) for enhanced brain delivery of antibody.

Antibody therapeutics are limited in treating brain diseases due to poor blood-brain barrier (BBB) penetration. We have discovered that poly 2-methacryloyloxyethyl phosphorylcholine (PMPC), a biocompatible polymer, effectively facilitates BBB penetration via receptor-mediated transcytosis and have developed a PMPC-shell-based platform for brain delivery of therapeutic antibodies, termed nanocapsule. Yet, the platform results in functional loss of antibodies due to epitope masking by the PMPC polymer network, which necessitates the incorporation of a targeting moiety and degradable crosslinker to enable on-site antibody release. In this study, we developed a novel platform based on site-oriented conjugation of PMPC to the antibody, allowing it to maintain key functionalities of the original antibody. With an optimized PMPC chain length, the PMPC-antibody conjugate exhibited enhanced brain delivery while retaining epitope recognition, cellular internalization, and antibody-dependent cellular phagocytic activity. This simple formula incorporates only the antibody and PMPC without requiring additional components, thereby addressing the issues of the nanocapsule platform and paving the way for PMPC-based brain delivery strategies for antibodies.

Nanofibrous TiO2 produced using alternating field electrospinning of titanium alkoxide precursors: crystallization and phase development.

High-yield, free-surface alternating field electrospinning (AFES) was effectively used in the fabrication of titanium oxide nanofibrous materials from the precursors based on titanium alkoxide and a blend of polyvinylpyrrolidone and hydroxypropyl cellulose. The alkoxide/polymer mass ratio in the precursor solution has significant effects on the precursor fiber production rate as well as the structure of resulting TiO2 nanofibers after thermal processing of precursor fibers at temperatures from 500 to 1000 °C. Within the range of tested process parameters, the best fiber production rate of ∼5.2 g h-1 was achieved, in terms of the mass of crystallized TiO2 nanofibers, with the precursor that corresponded to 1.5 : 1 TiO2/polymer mass ratio. TiO2 nanofibers produced by calcination at 500 °C for 3 h had 100-500 nm diameters and were composed of anatase (20-25 nm crystallite size) with rutile content 0.1-6.0 mol%, depending on the precursor composition. A considerable amount of anatase phase (up to 80 mol%) can be retained after thermal processing of TiO2 nanofibers at 750 °C for 3 h. A nanofibrous material composed of smooth and long, predominantly monocrystalline rutile, fibrous segments was produced at 1000 °C from the precursor with 2.5 : 1 TiO2/polymer mass ratio.